The present invention relates generally to methods and devices for drug delivery and analyte extraction, and specifically to medical methods and devices for puncturing the outer layer of living skin and to methods and devices for transdermal drug delivery and analyte extraction.
A number of different methods have been developed to perform transdermal drug delivery and/or analyte extraction, including passive diffusion of a drug or analyte between a skin patch and skin, as well as active processes such as iontophoresis, sonophoresis, electroporation, and chemically enhanced diffusion. These methods are primarily used for generating transdermal movement of small molecules, but generally do not enhance the motion of large molecules through the 10-50 micron thick outermost layer of the skin, the stratum corneum epidermidis.
In an article, xe2x80x9cMicromachined needles for the transdermal delivery of drugs,xe2x80x9d IEEE 11th Annual International Workshop on Micro-Electro-Mechanical Systems (1998), pp. 494-498, which is incorporated herein by reference, Henry et al. discuss a method of mechanically puncturing the skin with microneedles in order to increase the permeability of skin to a test drug. In the article, microfabrication techniques are described to etch an array of needles in silicon, and experiments performed on cadaver skin with the needle array demonstrated an increase in permeability subsequent to puncture of the skin. The needles are created with a predetermined length, and penetrate to the same depth from the skin surface, regardless of the local thickness of the stratum corneum. It is known that if the needles are longer than the local thickness, then the underlying epidermal tissue may be injured, while if the needles are too short, channel formation through the stratum corneum may be incomplete.
U.S. Pat. Nos. 4,775,361, 5,165,418, and 5,423,803, and PCT Publication WO 97/07734, the disclosures of which are incorporated herein by reference, describe methods of using laser pulses to locally heat the stratum corneum to about 120xc2x0 C., thereby causing local ablation, in order to cause a single hole to develop in the stratum corneum through which large molecules may pass. Whereas some selectivity of ablation depth can be attained by varying the wavelength of the laser pulse, no feedback mechanism is disclosed whereby the laser pulses are terminated upon generation of the necessary damage to the stratum corneum.
PCT Publication WO 97/07734 also discloses thermal ablation of the stratum corneum using an electrically resistive element in contact with the stratum corneum, such that a high current through the element causes a general heating of tissue in its vicinity, most particularly the stratum corneum. As above, no means are disclosed to terminate current flow upon sufficient disruption of the stratum corneum. Additionally, thermal characteristics of skin vary highly across different areas of an individual""s skin, as well as among a group of subjects, making optimal thermal dosages, which produce the desired ablation without causing pain, very difficult to determine. Lastly, increasing transdermal molecular flow by increasing the permeability of the stratum corneum, whether using microneedles, laser energy, or resistive heating of tissue, is inherently a two step process: (a) position apparatus to generate holes, and (b) apply a patch to the skin, through which the molecules will flow.
Electroporation is also well known in the art as a method to increase pore size by application of an electric field. This process is described in an article by Chizmadzhev et al., entitled xe2x80x9cElectrical properties of skin at moderate voltages,xe2x80x9d Biophysics Journal, February, 1998, 74(2), pp. 843-856, which is incorporated herein by reference. Electroporation is disclosed as a means for transiently decreasing the electrical resistance of the stratum corneum and increasing the transdermal flux of small molecules by applying an electric field to increase the size of existing pores. Electroporation generally does not produce pores of sufficient diameter to pass large molecules therethrough. Additionally, optimal voltage profiles are difficult to determine because of naturally occurring variations as described hereinabove, as well as the lack of an accurate feedback mechanism to indicate achievement of the desired pore enlargement. If excessive voltage is applied, an irreversible breakdown occurs, resulting in damage to the skin and possible sensations of pain.
U.S. Pat. No. 5,019,034 to Weaver et al., whose disclosure is incorporated herein by reference, describes apparatus for applying high voltage, short duration electrical pulses on the skin to produce electroporation, and states that xe2x80x9c . . . reversible electrical breakdown . . . along with an enhanced tissue permeability, is the characteristic effect of electroporation.xe2x80x9d
It is an object of some aspects of the present invention to provide improved apparatus and methods for transdermal delivery of an active substance.
It is a further object of some aspects of the present invention to provide improved apparatus and methods for transdermal analyte extraction.
It is yet a further object of some aspects of the present invention to provide improved apparatus and methods for creating narrow channels through the stratum corneum of living skin by puncturing.
It is still a further object of some aspects of the present invention to provide improved apparatus and methods for reducing sensation and minimizing damage to skin underlying the stratum corneum during channel creation.
It is an additional object of some aspects of the present invention to provide improved apparatus and methods for controlling the timing of channel creation.
It is yet an additional object of some aspects of the present invention to provide improved apparatus and methods for regulating channel creation responsive to properties of the skin.
It is another object of some aspects of the present invention to provide improved apparatus and methods for puncturing the skin and/or transdermally delivering an active substance and/or transdermally extracting an analyte, using a miniature, self-contained device.
It is yet another object of some aspects of the present invention to provide improved apparatus and methods for transdermally delivering an active substance using a standard medical skin patch.
In preferred embodiments of the present invention, a device for enhancing transdermal movement of a substance comprises: (a) a skin patch, with at least two electrodes in contact with the skin of a subject; and (b) a control unit, coupled to the patch, which causes a current to pass between the electrodes through the stratum corneum epidermidis, in order to generate at least one micro-channel in the stratum corneum to enable or augment transdermal movement of the substance. Preferably, the control unit comprises switching circuitry to control the magnitude and/or duration of the electric field at the electrode.
The term xe2x80x9cmicro-channelxe2x80x9d as used in the context of the present patent application and in the claims refers to a pathway generally extending from the surface of the skin through all or a significant part of the stratum corneum, through which pathway molecules can diffuse. Preferably, micro-channels allow the diffusion therethrough of large molecules at a greater rate than the same molecules would diffuse through pores generated by electroporation. It is believed that such micro-channels are formed due to local power dissipation leading to ablation of the stratum corneum when an electric field of sufficient magnitude is applied to a small area of the skin, in contact with the electrodes, for a certain period of time. Unlike methods of electrically-promoted drug delivery known in the art, such as iontophoresis and electroporation, the present invention enables relatively large channels to be formed, through which even large molecules of the active substance can pass rapidly, without the necessity of ionizing or polarizing the molecules.
The current flow between the electrodes can be described as having two components: (a) a perpendicular component, which is generally perpendicular to the skin surface (and, if the associated electric field is sufficiently large, may cause current to go through the stratum corneum into the underlying epidermal tissue and dermis); and (b) a lateral component, generally parallel to the skin surface, which remains generally within the stratum corneum. Substantially all of the current generated at one electrode ultimately emerges from the skin and is taken up by an adjacent electrode.
In preferred embodiments of the present invention, methods and/or apparatus are employed to increase the relative value of the lateral component with respect to the perpendicular component. In general, the stratum corneum epidermidis (the superficial layer of the epidermis) demonstrates a significantly higher resistance to the passage of molecules therethrough than does the underlying epidermal tissue. It is therefore an object of these preferred embodiments of the present invention to form micro-channels in the stratum corneum by ablating the stratum corneum in order to increase conductance of the substance therethrough, and to generally not directly affect or damage epidermal tissue underlying the stratum corneum or in the innervated dermis. Additionally, limiting current flow substantially to the non-innervated stratum corneum is expected to decrease or eliminate the subject""s sensations, discomfort, or pain responsive to use of the present invention, particularly as compared with other procedures known in the art.
A voltage applied between two electrodes on the skin generates an electric field that is to a large extent confined to the volume in a vicinity of the electrodes. Thus, electrodes which are widely spaced produce a fieldxe2x80x94and current flow responsive theretoxe2x80x94which extends relatively deep into the skin. Conversely, electrodes which are closely spaced do not generate significant current flow at deeper layers. Therefore, in some preferred embodiments of the present invention, the electrodes of the device are separated by distances smaller than about 100 microns (but for some applications by distances of up to approximately 500 microns), in order to generate a current flow which is largely confined to a thin layer, comprising most or all of the stratum corneum. This effectively results in a desired larger value of the ratio of the lateral component to the perpendicular component, as described hereinabove.
In some of these preferred embodiments of the present invention, a high-frequency AC current with an optional DC current added thereto is applied between the closely-spaced electrodes in order to generate lateral capacitive currents in the stratum corneum and to cause breakdown and micro-channel formation in the stratum corneum.
In some preferred embodiments of the present invention, the patch comprises an array of electrodes, preferably closely-spaced electrodes, which act together to produce a high micro-channel density in an area of the skin under the patch. Preferably, the control unit and/or associated circuitry sequentially or simultaneously evaluates the current flow through each electrode, or a subset of the electrodes, in order to determine when one or more micro-channels have formed responsive to the applied field. Responsive thereto, the control unit discontinues application of the field. Since the formation of a micro-channel is typically marked by a local drop in electrical resistance of the skin, the control unit may, for example, reduce the voltage or current applied at any electrode wherein the current has exceeded a threshold. By reducing current flow upon or shortly after micro-channel formation, the likelihood of skin burns or pain sensations is minimized.
In some preferred embodiments of the present invention, a relatively high voltage is applied to the electrodes initially, so as to induce formation of micro-channels through the skin. A property of the current flow is detected, and the current is reduced or terminated when the property reaches a predetermined threshold. Preferably, the detected property of the current flow is secondary to changes in a conduction property of the skin, responsive to formation of one or more micro-channels through the stratum corneum.
Alternatively or additionally, a time-varying voltage V(t), characterized, for example, by the formula V(t)=V0+ktn, is applied between a first electrode and a second electrode in the skin patch until a shut-off signal is generated. (Constants k and n are nonnegative.) Other forms of V(t) may include a sinusoid, an exponential term, or a series of pulses. A current I(t), flowing responsive to the applied field, is measured by the control unit, as described hereinabove. Calculations of the values of ∫I(t)dt, dI/dt and/or d2I/dt2 are frequently performed. Comparisons of I and/or ∫I(t)dt and/or dI/dt and/or d2I/dt2 with respective threshold values are used as indicators of micro-channel formation and/or to determine when to generate the shut-off signal for the electrodes.
Further alternatively or additionally, in embodiments in which V(t) is sinusoidal, the control unit preferably calculates changes in a phase shift between V(t) and I(t) during application of the electric field, and controls the field responsive to these changes. It is believed that cells in the stratum corneum demonstrate capacitance, which causes the phase shift, and that ablation of the stratum corneum decreases the capacitance and is evidenced by a decrease in the phase shift.
Still further alternatively or additionally, the total charge which is passed through the skin is limited by a capacitor, inductor, or other energy-storage device. An appropriate choice of values for these components sets an absolute maximum quantity of charge which can pass through the skin, and thus limits any damage that can be caused thereby.
In some preferred embodiments of the present invention, one or more of the electrodes comprise or are coupled to an electrically conductive dissolving element, where the dissolving rate is generally proportional to the current passing through the electrode. When a sufficient quantity of charge has passed through the dissolving element, the electrode ceases to conduct electricity. Thus, a maximum total charge, Qtotal, is associated with an electrode, such that current flows through the element for only as long as q(t)xc2xa7∫I(t)dt less than Qtotal. This serves as a safety feature, reducing the possibility of skin burns secondary to applied electric fields. Alternatively or additionally, the dissolving element is constructed so that it becomes non-conductive after a quantity of charge has passed therethrough which is sufficient to ablate the stratum corneum.
In some further preferred embodiments of the present invention, the electrodes are xe2x80x9cprintedxe2x80x9d directly on the skin, preferably by stamping or by employing a transfer patch of a conductive substance (such as, for example, a conductive ink containing silver grains). In applications of such embodiments of the present invention for transdermal drug delivery, the conductive substance preferably comprises a matrix holding the drug to be administered to a subject.
Preferably, the printed electrodes demonstrate a substantially complete loss of conductance therethrough upon ablation of the stratum corneum responsive to the applied electric field. Further preferably, each printed electrode comprises a material which is conductive only when current flowing therethrough remains below a threshold value. If the current exceeds the threshold, then thermal fusion of the material causes it to become largely nonconductive, i.e. the material acts as a fuse. Still further preferably, current continues to flow through the other electrodes until they reach the threshold current, at a time which is generally associated with the time required for ablation of the stratum corneum, as described hereinabove. In some of these embodiments, the control unit may be made substantially simpler than as described regarding other embodiments, and generally does not need other circuitry in order to determine whether to generate a shut-off signal.
In still further preferred embodiments of the present invention, two electrodes on the patch form a concentric electrode pair, in which an inner electrode generates a current which passes through the stratum corneum to an outer electrode surrounding the inner electrode. The distance between the inner and outer electrodes is preferably between about 50 and about 200 microns, in order to maintain the ratio of the lateral to the perpendicular component of the current at a high value, as described hereinabove.
In some preferred embodiments of the present invention, a conductance-enhancing substance, preferably comprising a conductive cream or ink, is applied to the skin in order to increase the ratio of the lateral to the perpendicular component of current flow. Alternatively or additionally, the conductance-enhancing substance comprises a composition with a high diffusion coefficient, which diffuses into the lipid layers of the stratum corneum and further augments the selective power dissipation therein, in order to ablate the stratum corneum with substantially little damage to the underlying tissue. In some applications, the substance has an electrical charge associated therewith, such that when a small lateral field is applied, lateral diffusion of the substance within the stratum corneum is enhanced (i.e., iontophoresis of the substance).
In some of these preferred embodiments which utilize a conductance-enhancing substance, the substance further comprises an active substance, for example, a pharmaceutical product, dissolved or mixed therein. Since breakdown of the stratum corneum is often associated with removal of the enhanced conductivity path afforded by the conductance-enhancing substance, it is preferable in many of these embodiments to use a substantially constant voltage source to generate current at the electrodes. Removal of the enhanced conductivity path will result in a desired reduced power dissipation in the stratum corneum (P=V2/R), since the voltage remains constant while resistance increases.
In other preferred embodiments of the present invention, ablation of the stratum corneum is accomplished using a current-limited source to power the electrodes. It is believed that the stratum corneum generally displays high electrical resistance, while epidermal tissue underlying the stratum corneum has significantly lower electrical resistance. Ablation of the stratum corneum (i.e., removal of the high-resistance tissue) is therefore associated with a net decrease of electrical resistance between the electrodes, and the power dissipated in the epidermis following electrical breakdown will decrease, typically proportional to the change in resistance (P=I2R).
Monitoring changes in voltage, current, and/or phase for each electrode in the control unit may require, in certain implementations, a significant amount of circuitry. Therefore, in some preferred embodiments of the present invention, the control unit comprises one or more clusters of electrodes, in which monitoring and control are performed for each cluster rather than for the individual electrodes therein. The cluster is preferably over a relatively small area of skin, for example, from about 1 mm2 to about 100 mm2, in which properties of the skin are assumed to be substantially constant.
In some preferred embodiments of the present invention, the device is a stand-alone device, which enables transdermal delivery of an active substance or enhances transdermal motion of an analyte. Alternatively, the device creates micro-channels as described hereinabove and is then removed from the skin, in order to enhance the transdermal delivery of a substance into or out of a commercially-available skin patch subsequently placed on the skin. In other preferred embodiments of the present invention, the device is an add-on to commercially available transdermal drug delivery/analyte extraction devices, and serves primarily to create the micro-channels in the stratum corneum, and optionally to act as a vehicle through which the substance may pass.
In some preferred embodiments of the present invention, handheld apparatus for transdermal drug delivery and/or analyte extraction comprises a handle or other housing, a control unit, electrodes, and an ablation surface. The apparatus is passed by the user over a selected region of the skin, such that the electrodes on the ablation surface ablate the stratum corneum. Preferably, the ablation surface is coupled to a wheel which rotates as it moves across the skin, causing the electrodes to repeatedly come into contact and out of contact with the skin. Alternatively, the ablation surface slides across the skin without the use of a wheel, such that some electrodes substantially continuously maintain contact with the skin as the ablation surface moves along the skin.
Preferably, the handheld apparatus comprises a mechanical disposition sensor, coupled to send a disposition sensor signal to the control unit responsive to motion of the apparatus. In a preferred embodiment, the mechanical disposition sensor comprises a linear or angular accelerometer. Preferably, the control unit controls current flow to one or more pairs of the electrodes based at least in part on information including the position or motion of the ablation surface. For some applications, the control unit assesses the speed of the handheld apparatus, as determined by the disposition sensor and informs the user whether the present speed is appropriate for proper operation of the apparatus.
Alternatively or additionally, the mechanical disposition sensor comprises a linear or angular position sensor. For applications in which the ablation surface is coupled to a freely-rotating wheel, the output of the angular position sensor is preferably used to indicate to the control unit when to pre-charge one or more capacitors which convey current to the electrodes, typically at a desired interval before the electrodes contact the skin. This technique may advantageously be used to improve the efficiency of the handheld apparatus by optimizing the utilization of a battery of the apparatus.
In a preferred embodiment, the handheld apparatus comprises an output unit coupled to the control unit, to enable the control unit to communicate pertinent information to the user. Preferably, the information comprises some or all of the following:
the operational status of the device,
an indication following successful ablation of the stratum corneum by one or more pairs of electrodes,
the number of micro-channels formed in the current application of the device, and
the amount of skin surface treated by the device.
In a preferred embodiment the output unit comprises a display, such as an LCD. Alternatively or additionally, the output unit comprises a speaker, preferably enabled to convey some of the information.
In some preferred embodiments, the handheld apparatus ablates the stratum corneum so as to prepare the skin for drug delivery or analyte extraction by a separate drug delivery unit or analyte extraction unit. For example, a standard skin patch containing a drug could be applied to the region of skin ablated by the handheld apparatus. Because ablation of the stratum corneum as provided by these embodiments typically produces essentially no sensation, the handheld apparatus preferably comprises means for demarcating the region of skin prepared by the device. The demarcation enables the user to place the drug delivery unit or analyte extraction unit on the correct region of skin. For example, the device may comprise an ink or dye reservoir and means for delivering the ink or dye to the surface of the skin region which was treated by the device.
In other preferred embodiments, the handheld apparatus is used both to prepare the skin for drug delivery and to deliver the drug to the surface of the prepared skin. Preferably, the handheld apparatus comprises a drug reservoir and means for delivering the drug to the surface of the skin. For example, a porous material may be placed between adjacent electrodes, and coupled to the drug reservoir by a conduit such that the drug can flow from the reservoir, through the porous material, to the skin. Typically, the porosity of the material is selected so as to transfer the drug to the skin at a desired rate.
Alternatively or additionally, the drug reservoir comprises a pressure sensor, a sensor for determining the amount of drug in the reservoir, and a pump coupled to the control unit. Typically, the control unit drives the pump, responsive to a signal from the pressure sensor and responsive to pre-programmed parameters, so as to control the rate and/or quantity of drug transferred to the ablated portion of the skin. In some preferred embodiments, the control unit actuates the display to show messages related to this process, e.g., xe2x80x9cDelivering drug,xe2x80x9d xe2x80x9cDelivery completed,xe2x80x9d and xe2x80x9cReservoir empty. Please refill.xe2x80x9d In another preferred embodiment, a pre-moistened patch containing the requisite amount of drug is affixed to the ablation surface before use. For example, a standard medical patch may be attached to the ablation surface, in a manner that allows the electrodes to protrude through the patch. After one use, the patch is typically discarded.
In a preferred embodiment, an application surface for applying the drug is coupled to the handle of the handheld apparatus. Preferably, the application surface is behind the ablation surface as the handheld apparatus is passed over the skin, such that drug stored in or near the application surface is conveyed to the ablated skin during the motion of the handheld apparatus. For example, the application surface may comprise a drug reservoir, a conduit and a porous material, affixed to the handheld apparatus, such that the porous material is held in contact with the skin behind the ablation surface. In this manner, the porous material delivers the drug to the ablated region as the apparatus is passed over the skin. Preferably, the application surface is held in contact with the skin, such that the porous material slides across the skin. Alternatively, the application surface is coupled to a wheel, such that the porous material rolls across the skin.
In a preferred embodiment, the drug is pre-applied to an adhesive strip which is rolled, sometimes several times, around a spool attached to the handle of the handheld apparatus. Preferably, the spool is behind the ablation surface, such that as the handheld apparatus is moved across the skin, the adhesive strip unrolls and adheres to the region of skin which was just ablated. In this manner, the drug on the strip is brought in contact with the ablated region of the skin. Preferably, a desired quantity of the drug is uniformly applied to the adhesive strip. Alternatively, the drug is applied at discrete points on the adhesive strip, and the adhesive strip is so aligned on the spool such that the drug is placed directly over the individual ablated areas in the stratum corneum. A preferred technique for aligning the drug-delivery spool with the ablation surface includes attaching the spool and the ablation surface to the handle with the aid of alignment pins and/or notches, such that the discrete regions where the drug occurs on the adhesive strip are automatically unrolled onto the ablations in the stratum corneum.
There is therefore provided, in accordance with a preferred embodiment of the present invention, a device for treating skin on the body of a subject, including:
a plurality of electrodes, which are adapted to be placed in contact with the skin and then moved across the skin while maintaining electrical contact with the skin; and
a power source, which is adapted to apply a current between two or more of the plurality of electrodes at the same time as the electrodes are being moved across the skin.
Typically, the power source is adapted to apply the current such that skin layers beneath stratum corneum epidermidis of the skin are substantially not ablated. Moreover, the power source is also typically adapted to apply the current so as to ablate stratum corneum epidermidis of the skin. For some applications, the power source is adapted to configure the current so as to ablate both the stratum corneum and, at least partially, a layer of the skin deeper than the stratum corneum.
In a preferred embodiment, the device includes a marking unit, adapted to apply a substance to the skin so as to demarcate a region of the skin to which the current is applied. Alternatively or additionally, the device includes one or more protrusive elements, adapted to press the skin so as to demarcate a region of the skin to which the current is applied.
Preferably, at least one of the electrodes is adapted to contact the skin to create a contact area having a characteristic length of between about 10 and 100 microns.
In a preferred embodiment, at least one of the electrodes includes a bipolar electrode. Alternatively or additionally, the two or more electrodes include a return electrode and two or more current-driving electrodes, and the power source is adapted to apply respective currents between each of the current-driving electrodes and the return electrode.
Preferably, the power source is adapted to apply the current in order to allow a substance to pass through the skin. For example, the power source may be adapted to apply the current in order to allow a substance to pass through the skin into the body of the subject. Alternatively or additionally, the power source may be adapted to apply the current in order to allow a substance to pass through the skin from within the body of the subject.
Preferably, the device includes a substance application unit, adapted to apply a substance to the skin at a site on the skin to which the current is applied.
In a preferred embodiment, the substance application unit includes:
a spool, adapted to rotate as the device moves across the skin; and
a substance application strip having the substance applied thereto, which strip is adapted to be disposed around the spool, so as to unwind from the spool as the device is moved across the skin, and so as to cover the site on the skin to which the current is applied.
Typically, the substance application strip includes an adhesive, adapted to hold the strip in contact with the skin.
Alternatively or additionally, the substance application unit includes:
a reservoir, adapted to contain a dose of the substance; and
a conduit, coupled to the reservoir so as to transport the substance to the site.
For some applications, the conduit is adapted to provide a desired flow rate of the substance. Alternatively or additionally, the substance application unit includes a porous material, through which the substance passes during transport to the skin, so as to provide a desired flow rate of the substance.
In a preferred embodiment, the substance application unit includes a pump, coupled to the reservoir, which is adapted to provide a desired flow rate of the substance.
There is further provided, in accordance with a preferred embodiment of the present invention, a device for treating skin on the body of a subject, including:
a roller, adapted to rotate when it is moved across the skin;
a plurality of electrodes, disposed over a surface of the roller, so as to be placed in sequence into contact with the skin as the roller is moved across the skin; and
a power source, which is adapted to drive a current through each electrode when the electrode is in contact with the skin.
There is still further provided, in accordance with a preferred embodiment of the present invention, a device for treating skin on the body of a subject, including:
a housing;
a plurality of electrodes, disposed on a surface of the housing, which are adapted to be placed in contact with the skin;
a motion sensor, which is adapted to generate a sensor signal responsive to motion of the housing; and
a control unit, which is adapted to receive the sensor signal, to determine, responsive thereto, a physical disposition of the device, and to control current flow to the plurality of electrodes responsive to determining the physical disposition.
Preferably, the control unit is adapted to determine a velocity of the device and to control the current flow to the electrodes responsive thereto. In a preferred embodiment, the control unit is adapted to terminate the current flow if the velocity is outside of a specified operating range.
Alternatively or additionally, the control unit is additionally adapted to determine a distance traveled by the device, and to control the current flow to the electrodes responsive thereto. In a preferred embodiment, the control unit is adapted to terminate the current flow after the device has traveled a specified distance.
Further alternatively or additionally, the control unit is adapted to determine an acceleration of the device and to control the current flow to the electrodes responsive thereto. In a preferred embodiment, the control unit is adapted to terminate the current flow if the acceleration is outside of a specified operating range.
Preferably, the device includes an output unit, coupled to the control unit, and the control unit is adapted to actuate the output unit to generate an output signal indicative to the subject of the physical disposition of the device. In a preferred embodiment, the output unit includes a speaker, and the control unit is adapted to actuate the speaker responsive to the physical disposition. Alternatively or additionally, the output unit includes a display, and the control unit is adapted to actuate the display responsive to the physical disposition. There is yet further provided, in accordance with a preferred embodiment of the present invention, a device for treating skin on the body of a subject, including:
a housing;
a plurality of electrodes, disposed on a surface of the housing, which are adapted to be placed in contact with the skin and to apply a current to the skin;
a motion sensor, which is adapted to generate a sensor signal responsive to motion of the housing;
an output unit; and
a control unit, which is adapted to receive the sensor signal, to determine, responsive thereto, a physical disposition of the device, and to actuate the output unit to generate an output signal indicative to the subject of the physical disposition of the device.
In a preferred embodiment, the control unit is adapted to determine a velocity or acceleration of the device, and to actuate the output unit to generate the output signal responsive to the velocity or acceleration of the device. Alternatively or additionally, the control unit is adapted to determine a distance traveled by the device, and to actuate the output unit to generate the output signal responsive to the distance traveled by the device.
There is also provided, in accordance with a preferred embodiment of the present invention, a device for causing a pharmaceutical substance to enter a bloodstream of a subject through a site on skin of the subject, including:
a housing;
a spool, coupled to the housing, which is adapted to rotate when the housing is moved across the skin; and
a substance application strip having the substance applied thereto, which strip is adapted to be disposed around the spool, so as to unwind from the spool as the housing is moved across the skin, and to cover the site on the skin, such that the pharmaceutical substance travels through the skin and enters the bloodstream.
Preferably, the device includes a plurality of electrodes, adapted to apply a current to sites on the skin, wherein the substance application strip is adapted to have the substance applied to discrete sites of the strip which correspond to the sites on the skin.
In a preferred embodiment, the substance application strip is divided into sections, wherein each section has a dose of the substance applied thereto, and wherein each section is arranged to be removed from the strip following unwinding of the section from the spool.
There is also provided, in accordance with a preferred embodiment of the present invention, a method for treating skin on the body of a subject, including;
placing a plurality of electrodes in contact with the skin;
moving the electrodes across the skin while maintaining their electrical contact with the skin; and
driving a current between two or more of the plurality of electrodes at the same time as the electrodes are being moved across the skin.
Preferably, driving the current includes configuring a parameter of the current such that skin layers beneath stratum corneum epidermidis of the skin are substantially not ablated by the current. Alternatively or additionally, driving the current includes configuring a parameter of the current such that stratum corneum epidermidis of the skin is ablated by the current.
In a preferred embodiment, the method includes applying a marking substance to the skin so as to demarcate a region of the skin to which the current is applied.
Driving the current includes driving the current in a bipolar mode. Alternatively or additionally, driving the current includes driving the current in a monopolar mode.
Preferably, driving the current includes configuring a parameter of the current so as to allow a substance to pass through the skin. Further preferably, the method includes delivering a substance into the skin at a site on the skin to which the current is applied. Alternatively or additionally, the method includes extracting a substance through the skin at a site on the skin to which the current is applied.
Preferably, the method includes applying an active substance to the skin at a site on the skin to which the current is applied. Applying the substance typically includes regulating a flow rate of the substance, for example, by actively pumping the substance.
There is additionally provided, in accordance with a preferred embodiment of the present invention, a method for treating skin on the body of a subject, including:
placing a plurality of electrodes in contact with the skin in sequence; and
driving a current through each of the electrodes when the respective electrode is in contact with the skin.
There is yet additionally provided, in accordance with a preferred embodiment of the present invention, a method for treating skin on the body of a subject, including:
placing a plurality of electrodes in contact with the skin;
determining a physical disposition of the electrodes; and
driving a current between two or more of the plurality of electrodes responsive to the disposition of the electrodes.
Preferably, driving the current includes driving the current responsive to a velocity or acceleration of the electrodes. Alternatively or additionally, driving the current includes driving the current responsive to a distance traveled by the electrodes. Preferably, the current is terminated responsive to the electrodes having moved a specified distance.
In a preferred embodiment, the method includes generating an audible or visual indication to the subject the physical disposition of the electrodes.
The method preferably includes applying a pharmaceutical substance to the skin at a site on the skin to which the current is applied.
There is still additionally provided, in accordance with a preferred embodiment of the present invention, -a method for treating skin on the body of a subject, including:
placing a plurality of electrodes in contact with the skin;
driving a current between two or more of the plurality of electrodes;
determining a physical disposition of the electrodes; and
generating an output signal indicative to the subject of the physical disposition of the electrodes.
Preferably, generating the output signal includes generating the signal responsive to a velocity or acceleration of the electrodes. Alternatively or additionally, generating the output signal includes generating the signal responsive to a distance traveled by the electrodes.
Preferably, generating the output signal includes generating an audible or visual signal.
There is yet additionally provided, in accordance with a preferred embodiment of the present invention, a device for treating skin on the body of a subject, including:
a plurality of receiving electrodes, which are adapted to be placed in contact with the skin so as to provide electrical contact with the skin;
a driving electrode, which is adapted to be passed across the receiving electrodes so as to create electrical contact with a first one of the receiving electrodes prior to creating electrical contact with a second one of the receiving electrodes; and
a power source, which is adapted to drive the driving electrode to apply a first current to the first receiving electrode when the driving electrode is in electrical contact with the first receiving electrode, and to apply a second current to the second receiving electrode when the driving electrode is in electrical contact with the second receiving electrode.
Preferably, the device includes a patch, fixed to the receiving electrodes, which patch is adapted to be applied to the skin.
In a preferred embodiment, at least one of the receiving electrodes includes a monopolar electrode.
Typically, the power source is adapted to drive the driving electrode to apply the first current at a magnitude sufficient to ablate stratum corneum of the skin.
The power source is also typically adapted to drive the driving electrode to apply the first current through the first receiving electrode into a site on the skin, and wherein the device includes a substance application unit, adapted to apply a substance to the skin at the site.